Polio endgame: Lessons for the global rotavirus vaccination program

Poliovirus and rotavirus share notable similarities. Although rotavirus is not amenable to eradication because of animal reservoirs, live, attenuated oral vaccines have been the bedrock of both prevention and control programs, providing intestinal and humoral immunity. Both programs have also encountered safety concerns and suboptimal immune responses to oral vaccines in low-income settings that have been challenges, prompting the search for alternative solutions. In this paper, we review the progress made by polio prevention and eradication efforts over the past six decades. Specifically, we discuss the roles of the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) in achieving polio eradication, and explore potential application of these lessons to rotavirus. Recent scientific evidence has confirmed that a combined schedule of IPV and OPV adds synergistic value that may give the polio eradication effort the tools to end all poliovirus circulation worldwide. For rotavirus, oral vaccine is the only currently licensed and recommended vaccine for use in all children worldwide, providing heterologous protection against a broad range of strains. However, parenteral rotavirus vaccines are in the pre-clinical and clinical trial stage and insight from polio provides strong justification for accelerating the development of these vaccines. While challenges for parenteral rotavirus vaccines will need to be addressed, such as achieving protection against a broad range of strains, the principle of combined use of oral and parenteral rotavirus vaccines may provide the necessary humoral and intestinal immunity necessary to close the efficacy gaps between developing and developed countries, therefore controlling rotavirus worldwide. This strategy may also potentially reduce risk of intussusception.     

Polio vaccination coverage and seroprevalence of poliovirus antibodies after the introduction of inactivated poliovirus vaccines for routine immunization in Japan

In Japan, the oral poliovirus vaccine (OPV) was changed to 2 types of inactivated poliovirus vaccine (IPV), the standalone conventional IPV (cIPV) and the Sabin-derived IPV combined with diphtheria-tetanus-acellular pertussis vaccine (DTaP-sIPV), for routine immunization in 2012. We evaluated polio vaccination coverage and the seroprevalence of poliovirus antibodies using data from the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) from 2011 to 2015. Several years before the introduction of IPV in 2012, OPV administration for children was refused by some parents because of concerns about the risk of vaccine-associated paralytic poliomyelitis. Consequently, in children aged <1?years who were surveyed in 2011–2012, polio vaccination coverage (45.0–48.8%) and seropositivity rates for poliovirus (type 1: 51.7–65.9%, type 2: 48.3–53.7%, and type 3: 15.0–29.3%) were decreased compared to those surveyed in 2009. However, after IPV introduction, the vaccination coverage (95.5–100%) and seropositivity rates (type 1: 93.2–96.6%, type 2: 93.1–100%, and type 3: 88.6–93.9%) increased among children aged <1?years in 2013–2015. In particular, seropositivity rates and geometric mean titers (GMTs) for poliovirus type 3 in <5-year-old children who received 4 doses of IPV (98.5% and 247.4, respectively) were significantly higher than in those who received 2 doses of OPV (72.5% and 22.9, respectively). Furthermore, in <5-year-old children who received 4 doses of either DTaP-sIPV or cIPV, the seropositivity rates and the GMTs for all 3 types of poliovirus were similarly high (96.5–100% and 170.3–368.8, respectively). Our findings from the NESVPD demonstrate that both the vaccination coverage and seropositivity rates for polio remained high in children after IPV introduction.     

首剂IPV纳入免疫规划后儿童家长的认知及态度分析

目的了解首剂脊灰活疫苗(IPV)纳入免疫规划后儿童家长的认知及态度,为制定脊灰疫苗免疫策略调整后的实施措施提供参考。方法对2016年7—12月白云街道社区卫生服务中心预防接种门诊接种脊灰疫苗儿童的家长开展问卷调查,并对在此期间参加妈妈班的家长进行个案访谈。结果本次共调查了532人,95.86%的家长知道脊灰减毒活疫苗(糖丸),76.88%认为糖丸是不安全的疫苗,21.43%的家长知道首剂IPV纳入免疫规划政策,16.73%的家长知道2价脊灰与糖丸的区别,81.39%的家长愿意按IPV+b OPV程序接种。多数家长表示赞同首针接种IPV的免疫策略。结论首剂IPV纳入免疫规划后多数家长不了解首针接种脊灰灭活疫苗的免疫策略及其意义,担心疫苗安全问题,建议进一步加强脊灰转换策略相关知识的宣传工作。     

sIPV process development for costs reduction

Polio is expected to be eradicated within only a few years from now. Upon polio eradication, the use of oral polio vaccines, which can cause circulating and virulent vaccine derived polio viruses, will be stopped. From this moment onwards, inactivated polio vaccines (IPV) will be used for worldwide vaccination against polio. An increased demand for IPV is thus anticipated. As a result, process development studies regarding the IPV production process, developed in the 1960s, have intensified. Studies on yield optimization aiming at costs reduction as well as the use of alternative polio viruses, which are more biosafe for manufacturing, are actual. Here our strategy to setup a new IPV production process using attenuated Sabin polio virus strains is presented. Moreover, aspects on reduction of the costs of goods and the impact of process optimization on sIPV costs are reviewed.     

灭活脊髓灰质炎病毒疫苗在中国应用的咨询意见调查

目的从扩大免疫规划（Expanded Program on Immunization,EPI）专家认知,来探讨灭活脊髓灰质炎（脊灰）病毒疫苗（Inactivated Poliovirus Vaccine,IPV）在中国应用的相关问题,为制定脊灰疫苗免疫策略提供参考。方法以人口数多和疫苗需求量大为原则,在全国范围内选取7个省（自治区）,对30名EPI专家进行开放式问卷调查。结果50％的调查对象希望在2015年国家能将IPV纳入EPI,与世界卫生组织提出的{2013～2018年消灭脊灰终结战略计划》时间进度表同步,专家们一致认同在保证疫苗质量的前提下,应尽可能地降低疫苗成本,IPV可接受价格中位数为20元／剂（范围5～50元／剂）。实现IPV国产化势在必行,卫生行政等政府部门应尽快明确中国脊灰疫苗免疫策略和使用时间进度表,疾病预防控制中心依据卫生行政部门制定的免疫策略提供技术指导和支持,疫苗生产企业应加快IPV的研发、生产和上市。结论EPI专家一致赞同随着全球消灭脊灰的进程,中国逐步引入IPV是大势所趋。     

An inactivated poliovirus vaccine using Sabin strains produced on the serum-free PER.C6® cell culture platform is immunogenic and safe in a non-human primate model

BackgroundThe World Health Organization recommends the development of affordable next-generation inactivated poliovirus vaccines (IPV) using attenuated poliovirus Sabin strains. Previously, we introduced a novel PER.C6® cell culture platform, which allows for high yield production of an affordable trivalent Sabin IPV vaccine.MethodsImmunogenicity and safety of this novel PER.C6®-based Sabin-IPV (sIPV) was assessed in rats and non-human primates (NHPs). NHPs received one of four different dose dilutions vaccine according to current human schedule (three prime-immunizations and one boost immunization). For comparison, NHPs received commercially available reference Salk IPV or sIPV.ResultsDose-dependent immunogenicity and good tolerability was observed for the PER.C6®-based sIPV formulations in rats and NHPs. In NHPs, the lowest tested dose that induced anti-Sabin virus-neutralizing antibody titers that were non-inferior to commercial sIPV after three immunizations was 5-7.5-25 D-antigen units for type 1, 2 and 3 respectively.DiscussionPER.C6®-based sIPV induced comparable immunogenicity to commercial Salk IPV and sIPV vaccines in NHPs. Together with the absence of any preclinical safety signals, these data warrant further testing in clinical trials. sIPV produced on the PER.C6® cell platform could be one solution to the need for an affordable and immunogenic IPV to achieve and maintain global polio eradication.     

脊髓灰质炎疫苗应用现状及免疫策略进展

1988年,全球消灭脊髓灰质炎（脊灰）倡议行动启动以来,取得了重大进展。2012年,全球报告脊灰223例,较2011年减少〉60%,本土脊灰流行国家减少为尼日利亚、巴基斯坦和阿富汗,脊灰野病毒（Wild Poliovirus,WPV）病例数下降到历史最低水平。但WPV传播仍未被阻断,无脊灰国家/地区仍面临输入WPV的风险。同时,有些国家正面临使用口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）所致疫苗衍生脊灰病毒的风险。目前,不同国家/地区评估各自的脊灰发病风险,依据OPV、脊灰病毒灭活疫苗（Inactivated Poliovirus Vaccine,IPV）的风险和收益,不同国家/地区采用不同的免疫策略：仅使用IPV、序贯使用IPV/OPV和仅使用OPV。2013年,世界卫生组织《全球消灭脊灰终结战略计划》中提出,2014年全球阻断WPV传播,2015年所有国家应至少使用1剂IPV,停用OPV中的Ⅱ型组分;2018年完成消灭WPV证实后,停用OPV。现对OPV和IPV的应用现状以及免疫策略进行简述。     

A mucosal adjuvant for the inactivated poliovirus vaccine

The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV.     

Adjuvants and inactivated polio vaccine: A systematic review

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV.     

Polio vaccines: WHO position paper,January 2014 – Recommendations

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of polio vaccination from the WHO position paper on polio vaccines – January 2014 recently published in the Weekly Epidemiological Record [1]. This position paper summarizes the WHO position on the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunization schedules as a strategy to mitigate the potential risk of re-emergence of type 2 polio following the withdrawal of Sabin type 2 strains from oral polio vaccine (OPV). The current document replaces the position paper on the use of polio vaccines published in 2010 [2].     

CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus

Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.     

Immune response to an intercalated enhanced inactivated polio vaccine/oral polio vaccine programme in Israel: impact on the control of poliomyelitis

A combined enhanced inactivated polio vaccine (EIPV) and oral polio vaccine (OPV) programme was introduced in Israel in 1990, with the purpose of providing a solution to the persistent polio morbidity in spite of a 30 year long OPV programme. The schedule comprised two doses of EIPV administered at the age of 2 and 4 months, intercalated with two doses of OPV at 4 and 6 months, followed by a reinforcing dose with the two vaccines simulltaneously administered at 12 months. The 5-year evaluation of the programme included: the assessment of clinical suspicions of polio, early immune response in successive cohorts administered the new schedule, dynamics of the immune profile in a cohort followed up to the age of 5, and monitoring of wild poliovirus excretion in sewage specimens collected in 25 permanent sites throughout Israel as well as from the Palestinian Authority. No paralytic polio cases associated with a wild or vaccinal poliovirus strain were detected since the introduction of the programme. At the age of 4 months, one week after administration of the second EIPV and first OPV dose, 100% seropositivity and high geometric mean titres (GMTs) of neutralizing antibody (NA) to the three vaccinal and to the wild poliovirus type 1, responsible for the 1988 polio outbreak, were observed. No change in percent of seropositivity occurred between the age of 6 and 12 months. Thirty days after the IPV and OPV reinforcing doses, GMTs to each of the four poliovirus strains were ≥3037. Up to the age of 5, the seropositivity was unchanged. After a 2.5–10-fold decline in the first year following the completion of the programme, GMTs to the three vaccinal and the wild poliovirus strain levelled off at rather high values, considered protective. Between 1990 and 1995, 16 wild poliovirus type 1 strains were isolated in three separate episodes in Gaza Strip sewage and once only in one Israeli site very close to Gaza City. The rapidly established, high and persistent NA titre to the vaccinal and wild poliovirus strains and the presence of immunological memory are indicative of high individual protection throughout the first 5 years of life. The only one-time introduction, without circulation, of a wild poliovirus strain in a single Israeli settlement suggests community protection. The intercalated programme offers a contribution to polio eradication by providing a solution to the primary and secondary failure associated with POV, as well as to the control of vaccine-associated paralytic poliomyelitis.     

PER.C6 cells as a serum-free suspension cell platform for the production of high titer poliovirus: A potential low cost of goods option for world supply of inactivated poliovirus vaccine

There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries.     

Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial

BackgroundThe Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.MethodsBetween May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.FindingsWe randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was −3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of −10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.ConclusionsNeither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.     

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation,an open label,phase IV,randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age.MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age.FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C.InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.     

Polio: The Disease that Reemerged after Six Years in Ethiopia

BackgroundPolio is a disabling and potentially deadly disease caused by a wild poliovirus and vaccine-derived poliovirus. The purpose of this review is to discuss the current situation of polio in Ethiopia.MethodRelevant scientific articles on Polio were searched from different data bases and websites.ResultsThe first wild poliovirus in Ethiopia was detected in 1999, followed by detection of few cases in 2000 and 2001. No wild poliovirus was detected in Ethiopia for the next 3 years (2001–2003). However, the disease resurged again in the country between 2004 and 2008 due to challenge to provide sufficient oral poliovirus vaccine coverage, migration and cross border economic activities and lack of good acute flaccid paralysis surveillance. After almost 5 years with no wild polio virus, Ethiopia again affected by polio outbreak importation in 2013. However, due to multiple supplementary immunization activities campaigns of improved quality and enhanced surveillance, the outbreak was eventually successfully interrupted within 6 months of confirmation. The most recent emergence of polio in Ethiopia has seen in this year (2020) six years after the country documented zero polio cases since 2014. The cause of the resurgence of the disease is circulating vaccine derived polio virus-2. Currently, Ethiopia has been conducting outbreak response by declaring Mop-up campaigns since September 2020.ConclusionsTherefore, it can be recommended that: - 1. The country has to completely shift from oral polio virus vaccine to inactivated polio vaccine so that the risk of vaccine derived polio will be diminished; 2. Ethiopia has to strengthen the mop up campaign that it has started in September 2020 following the reemergence of the disease in the country; 3. Ethiopia has to strengthen surveillance for acute flaccid paralysis in order to rapidly detect any new virus importation and to facilitate a rapid response.     

以吸附无细胞百日咳-白喉-破伤风疫苗为基础的联合疫苗研究进展

吸附无细胞百日咳疫苗、白喉和破伤风类毒素联合疫苗（Adsorbed Acellular Pertussis Vaccine,Diphtheria Toxoid＆Tetanus Toxoid Combined Vaccine,DTaP）已有30多年的使用历史。将DTaP与乙型肝炎疫苗（Hepatitis B Vaccine,HepB）、脊髓灰质炎灭活疫苗（Inactivated Poliovirus Vaccine,IPV）和b型流行性感冒嗜血杆菌结合疫苗（Haemophilus Influenzae Type b Conjugate Vaccine,Hib）等制备成为联合疫苗使用,可以减少接种剂次,提高受种者的依从性,从而提高疫苗接种率。但是,联合疫苗不是几种疫苗简单地混合,在将DTaP与其他疫苗联合的过程中面临许多技术挑战,如DTaP与Hib联合存在Hib免疫原性降低的问题,DTaP与HepB联合存在免疫程序不统一和HepB免疫持久性的问题,DTaP与IPV联合时,其中的防腐剂柳硫汞会降低IPV的免疫原性的问题等。现就DTaP与这些疫苗联合时所面临的技术挑战、目前的研究进展和未来发展方向作一综述。     

Polio vaccines: WHO position paper,March 2016–recommendations

This article presents the World Health Organization’s (WHO) recommendations on the use of polio vaccine excerpted from the WHO position paper on polio vaccines – March 2016, published in the Weekly Epidemiological Record [1]. This position paper on polio vaccines replaces the 2014 WHO position paper [2]. The position paper summarizes the WHO position on the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunization schedules as a strategy to mitigate the potential risk of re-emergence of type 2 polio following the withdrawal of Sabin type 2 strains from oral polio vaccine (OPV) [3].Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO’s current position on the use of vaccines in the global context. This position paper reflects the global switch from trivalent to bivalent OPV which took place in April 2016. Recommendations on the use of polio vaccines have been discussed on multiple occasions by SAGE, most recently in October 2016; evidence presented at these meetings can be accessed at: http://www.who.int/immunization/sage/previous/en/index.html.     

Inactivated poliovirus vaccine and the final stages of poliovirus eradication

The use of the inactivated poliovirus vaccine (IPV) will increase before and probably also after the global eradication of the wild type poliovirus. Before eradication, the switch from the use of oral poliovirus vaccine (OPV) to IPV has been due to the better safety record of IPV. Introduction of IPV in the regular immunisation schedules is made easier by the development of several combination vaccines, including IPV. Maternal antibodies and young age, often considered problematic for early initiation of IPV schedules, did not compromise optimal maintenance of seropositivity during infancy or long-term persisting antibody levels in our studies. OPV-derived, potentially pathogenic and transmissible poliovirus strains, excreted by some individuals for years, may present a problem for a blunt stopping of all polio immunisations after eradication. Our recent results suggest that locally excreted IgA might have a role in the elimination of poliovirus infection in the intestinal tissues.     

The cost-effectiveness of alternative polio immunization policies in South Africa

AIMS: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. METHODS: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. CONCLUSIONS: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39.